Dual-Purification Analysis Device for Low-Concentration Substance Quantification

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for quantifying low-concentration physiologically active substances in clinical laboratory settings face challenges in measurement precision, throughput, and device installation area due to manual handling, contamination, and inefficient purification processes.

Innovation Solution

An analysis device with a dual-purification system using antigen-antibody reactions and mass spectrometry, featuring a specimen concentration disk with antibody magnetic beads and a solid-phase extraction cartridge disk, allowing offline processing and improved sample handling to enhance precision and throughput without increasing device size.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual handling methods are used for specimen processing and antibody magnetic bead operations, then device complexity is reduced, but measurement precision deteriorates due to operator variability and contamination

Engineering Contradiction:
Improvequantification accuracyVSAvoidautomation system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system performs automatic specimen processing, antibody magnetic bead operations, and data analysis without operator intervention. The automated apparatus handles all steps from specimen reception through quantification result output, eliminating manual handling variability and contamination risks while maintaining manageable device complexity through integrated automation

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical operations are replaced with automated mechanical systems. The automated apparatus uses programmed mechanical movements for specimen transfer, magnetic bead manipulation, and reagent addition, replacing operator-performed mechanical actions with precision-controlled automated mechanisms that improve measurement precision

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If single-stage purification using only antibody magnetic beads is used, then device complexity is minimized, but measurement precision deteriorates due to insufficient removal of interfering substances

Engineering Contradiction:
Improvequantification accuracyVSAvoidpurification system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The purification process is divided into two distinct stages: first-stage purification using antibody magnetic beads to capture target substances, and second-stage purification using solid-phase extraction cartridges to remove interfering substances. This segmentation allows each purification stage to specialize in removing specific types of contaminants, achieving superior measurement precision without excessive device complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The solid-phase extraction cartridge acts as an intermediary purification stage between the antibody magnetic bead capture and the final mass spectrometry analysis. This intermediate purification step removes interfering substances that survive the first purification stage, enhancing measurement precision by ensuring cleaner samples enter the detection system

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If online continuous processing is used for specimen purification and analysis, then productivity is improved, but measurement precision deteriorates due to carryover contamination between specimens

Engineering Contradiction:
Improvequantification accuracyVSAvoidthroughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The system extracts and removes the purified specimen from the continuous flow path after completion of purification steps, placing it in a separate container before mass spectrometry analysis. This extraction breaks the continuous online processing chain, preventing carryover contamination between specimens while maintaining high productivity through efficient batch processing and automated specimen handling

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system employs disposable consumables including antibody magnetic beads and solid-phase extraction cartridges that are discarded after single use. This approach prevents cross-contamination between specimens by ensuring each specimen contacts fresh, uncontaminated reagents and surfaces, maintaining measurement precision while supporting high throughput through rapid disposal and replacement of consumables

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Measurement precision

If multiple purification stages are implemented, then measurement precision is improved, but device installation area increases due to additional components

Engineering Contradiction:
Improvequantification accuracyVSAvoiddevice footprint
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The system merges multiple purification functions into a single integrated automated apparatus. Both the antibody magnetic bead-based first purification stage and the solid-phase extraction cartridge-based second purification stage are combined in one device, allowing two-stage purification to be performed without requiring separate standalone systems, thus improving measurement precision while limiting increase in device footprint

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The automated apparatus is designed with multi-functionality to perform specimen reception, two-stage purification, and mass spectrometry analysis within a single device. This universal design consolidates multiple functions that would otherwise require separate equipment, enabling improved measurement precision through multi-stage purification without proportionally increasing device installation area

Inventive Principle:
Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The device enables accurate and high-throughput quantification of low-concentration substances, reducing contamination and labor, and optimizing device layout for clinical applications.

Implementation Method 1

by adding and reacting antibody magnetic beads immobilized with an antipeptide antibody and an internal standard substance labeled with a stable isotope to peptide which is a subject component to be measured, the peptide which is the subject component to be measured and the internal standard substance are bound to the antibody magnetic beads

Methodology Applied
Scientific EffectAntigen-antibody reaction:

Implementation Method 2

a treated specimen is introduced to a device which can concentrate the subject component to be measured and detect by mass spectrometry

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 3

The concentrated peptide is ionized using an electrospray ionization method (ESI), to perform analysis using liquid chromatography/mass spectrometry (LC-ESI-MS)

Methodology Applied
Scientific EffectElectrospray ionization:

Data Source

PatentEP2543994B1Analysis device
Publication Date: 2018.11.14 HITACHI HIGH TECH CORP
  • EP2543994B1 patent drawingFigure 1
  • EP2543994B1 patent drawingFigure 2
  • EP2543994B1 patent drawingFigure 3~4

AI summary

Disclosed is an analysis device which can analyze substances with low blood concentration with high precision without having to make the device larger. The analysis device is composed of: a specimen disk equipped with specimen containers; a reagent disk equipped with reagent containers; a first disk equipped with first containers where purification of the subject component to be measured in the specimen is carried out; a second disk equipped with second containers where purification of the sample purified in the first container is carried out; and a mass spectrometry unit which measures the specimen purified in the second container.